Scientific Method —

Profits over your dead body

Health regulatory and advocacy groups are deliberately corrupted.

Imagine living in a world where visiting the doctor was an experience fraught with danger. Where the drugs you were prescribed may or may not be effective—and may or may not be safe. Imagine having a medical procedure recommended that wasn't known to work.

Up until the beginning of the 20th century, that was the case. People feared doctors, and rightly so, as bringers of death. But now, medicines and medical practice are tightly regulated, and a visit to the doctor is unlikely to result in septicaemia, or some other -emia that results in green goo bursting out of a limb. Nevertheless, certain practices have crept into healthcare that, on aggregate, have led to the early deaths of large numbers of people.

Now, the conspiracy minded among you might be thinking of cartoon villains covering up dastardly poison pills, but this is not actually the case. Ben Goldacre, a physician who writes the Bad Science blog, has now made a comprehensive catalog of these practices published in a book called Bad Pharma. In examining the healthcare industry, he paints a complicated picture in which almost all the actors are both bad guys and good guys. It can be read as a stinging rebuke, but more than anything it's criticism from someone who appreciates everything modern medicine has done—but wants to see it do even better.

Your GP is your friend, right?

Goldacre takes the medical community apart piece by piece. Take, for example, your friendly general practitioner. How old are they? When did they leave medical school? How up to date is their medical knowledge? Typically, a doctor's continuing education is an ad hoc thing, until recently, driven by their own motivation to stay current. Now, let's compound the problem: as a doctor, you are offered this very expensive week-long course on, say, the latest in blood pressure control medication. Alternately you can go on a free course. It just so happens that the free course is funded by a drug company, and guess whose drugs take center stage at that course?

Most GPs will take the free course. From the time your GP leaves medical school, they are likely to be given biased information on the effectiveness of drugs, making it difficult for them to make good clinical decisions. And, demonstrating a wonderful lack of self-awareness, most will insist that these sponsored courses and visits by drug representatives do not influence their own prescribing decisions. Even funnier, they do believe that the events influence the doctor next door.

But drugs work, don't they?

Surely the drugs on the market have been shown to work, you cry. Unfortunately, the story is not so simple, and Bad Pharma explains why. To get a drug on the market, you only have to show that it is better than a placebo. Drugs are almost never compared against the current best treatment. And when you do make such a comparison, it can sometimes seem like it is pretty close to random chance that decides whether the older or newer treatment is more effective.

To ensure that their drug makes it on to the market, drug companies can run multiple trials, and then simply present the data from the trial that shows a positive result—the rest never sees the light of day. Well, okay, it is not quite that simple, but it is true that negative results aren't put forward for public scrutiny, and that drug companies have a history of misleading regulatory authorities with trial data. The companies work to ensure that a drug stays on the market for as long as its patent is valid.

It is even worse than that though. Often you want to know whether the drug treats the underlying condition. But that can be very difficult to measure, so we end up using proxies. For instance, if you are treating a heart condition, then what you want to measure is whether the drug extends the life of the patient. But that takes years to test so a proxy like blood pressure is substituted. If a treatment lowers blood pressure, it must be doing good. That conclusion, however, should be regarded as tentative. To make certain that a drug actually works, those long-term mortality studies must be conducted.

That means that the drugs that you are prescribed are usually not known to be the best treatment. Some may be, but others are, at best, better than doing nothing. Bad enough? Wait, because Goldacre has more. The other side of the coin are a drug's side effects. Before a drug goes on the market, it get tested in up to a few thousand people. This is actually not enough to detect side effects that are either rare, or common within sub-populations.

This comes as no surprise to many people. The problem, however, lies in the lack of follow-through. Often a drug is allowed on the market under the condition that there will be follow up studies that will examine side effects and confirm its effectiveness. Yet those studies are likely to vanish without trace. Indeed, even though medical journals now explicitly welcome negative findings, studies that find a treatment doesn't work are about five times less likely to be published.

This publication bias is important. Imagine that you were a doctor who kept up to date by reading the medical literature—as every good doctor should. No doctor, however, can read all the literature, so they are likely to read systematic reviews, like those offered by Cochrane. However, a systematic review is only as good as the data the reviewers can get hold of—and, as we've just said, that's distorted.

The regulator knows what's best

Amazingly enough, regulatory bodies often have information on safety and efficacy they do not share with the likes of Cochrane. Indeed, they are just as likely to keep the results of studies secret. The European regulatory authority withheld data for a set of drugs for several years on spurious grounds, before getting smacked down by its ombudsman.

It is truly shocking that such poor behavior is simply accepted as normal. The authorities are the only people who can compel a drug company to release data, yet they often don't—and if they won't do it, you can imagine that the drug companies won't volunteer it.

The unhappy situation, according to Goldacre, is that the regulators in the US and Europe have been captured by the pharmaceutical industry. Which is not to say that they don't do their job in determining if a drug should go on to the market. But they have become extremely reluctant to take a drug off the market when it has been found to be harmful or not beneficial.

One of the issues that makes this possible is that the same body of people that makes the decision to allow a drug onto the market is the one that must take it off. Essentially, they have to admit that they are wrong. You try standing up in front of 300 million people and saying "Yeah, sorry that painkiller you have been taking and believe is fantastic? It could give you a heart attack and you aren't going to be able to purchase it anymore."

Patients with no patience

You might think that patient advocacy groups would remain your friend—surely the asthma society will advocate on behalf of asthma patients, right? But as Goldacre describes it, not necessarily. Patient advocacy groups also receive money from pharmaceutical companies, though they never declare this as explicitly as they do the donations from generous individuals or charity fundraisers.

It seems that there is sometimes a correlation between a patient advocacy group's position on a drug and its source of funding. If that is a coincidence, then I am in for some serious hat eating.

There is also the other side of this coin as well, where patients turn up demanding that insurance companies or national health providers fund a particular medication, even though the evidence for the medication's effectiveness might be extremely weak. Yet these patients seem driven to believe that this is the drug they need. The patients seem to get access to major newspapers and television programs, spurring these people on. Almost like the patients had PR agents.

And, as if that weren't enough

Then, of course, there is advertising. Drug companies love to complain about the cost of R&D. Yet advertising costs contribute more to the cost of a pill than R&D. That advertising gets combined with constant visits from drug company representatives, paid speaking engagements, free conference attendance, and sponsored workshops. Let's just say that the industry thinks it money well spent.

But advertising in the healthcare industry should not be thought of in the same way as car or computer advertising. When you get right down to it, buying the wrong computer is unlikely to shorten your life. Treatment decisions truly effect quality and length of life. Doctors and patients need accurate and complete information about a treatment to make an informed decision.

If complete information were available, then doctors would have a much better sense of which treatments were most effective and what their side effects were. And, in this ideal world, treatment would take the patient into consideration. For instance, the most effective drug might have an elevated risk of heart attack—acceptable for a young fit person, but not for someone who already has heart problems—meaning that a slightly less effective drug might be safer for some.

Medical advertising is, in fact, aimed at subverting these sorts of informed decisions. Drug companies want their drug prescribed, independent of whether it actually works or not.

I know, this is obvious, and is the purpose of advertising. But this is advertising that you pay for in several ways. It increases the cost of medical insurance, because doctors prescribe more expensive and less effective treatments. It increases the cost of drugs directly, since that advertising has to be paid for. Most importantly, treatment decisions driven by advertising will sometimes reduce the length and quality of your life.

Nothing to see here, move along

The pharmaceutical industry will try to tell you that these problems are problems of the past. For example, there is now a clinical trial database that ensures that each trial is known about, so that it is possible to infer negative results based on the lack of publication. Indeed, several major medical journals have publicly stated that they will not publish results from clinical trials that haven't been registered. Yet, Goldacre reports that some 20 percent of trials published in these journals in 2010 (after the database was up and running and the agreement made) were not on the register: journals are not doing due diligence.

And in the ultimate dose of fail, there is no one group responsible for curating these databases. So, yes, most trials are registered, but no one checks to see if they have reported back. I think that might be referred to as hiding failure in plain sight.

On publishing Bad Pharma, Ben Goldacre wisely included an afterword in which he tried to anticipate how industry groups would respond. I must say that he has, sadly, anticipated them well. Industry associations have been particularly Orwellian in this regard, claiming that the failed attempts to fix these problems—the failures are documented in the book itself—have, in fact, worked. It is as if they only read the chapter headings and then grabbed a set of scripted responses without checking to see if anyone else had read and anticipated the script.

I guess, for them, this is an attack on the industry as a whole. Which it is, but it is an attack made by someone who deeply appreciates all the good that modern medicine has done, and wants it to get better. Goldacre is not a conspiracy minded nutcase who sees bad guys behind every garbage can. No, he sees a system that has, despite some really perverse incentives, produced some blindingly good products. But those incentives also allow life-threateningly poor decisions to be rewarded, and that needs to change.

Goldacre's encouraging outlook is why each chapter ends with a list of what you, personally, can do to help. Questions you can ask your doctor if you are a patient. Things you can do as a doctor. What academics can do, what pharmaceutical companies can do.

Read this book. It will make you mad, it will make you scared. And, hopefully, it will bring about some change.

Listing image by Shutterstock

Chris Lee
Chris writes for Ars Technica's science section. A physicist by day and science writer by night, he specializes in quantum physics and optics. He lives and works in Eindhoven, the Netherlands. Emailchris.lee@arstechnica.com//Twitter@exMamaku

169 Reader Comments

Use to work in the Pharma industry. Was amazed to learn that the company that I worked for (~35000 employees) had 3500 VPs. Yes, one out of every 10 employees was a VP. Include those above VP and this constitutes roughly 15% of the employees. Now factor in the typical big business "Senior Management brings soooo much to us and we must reward them accordingly" mindset.

Result: Roughly 30% of all cash revenues MUST be given to Senior Management in the form of compensation, bonuses, stock options, perks, etc and there is not a lot left for the shareholders. (Look at Medicare versus private Insurance administrative costs ~3% versus ~35%).

(Side note: This is the objective of every effort to privatize any and everything of monetary worth in the public sector - Senior Management gets its 30-35% with privatization)

All hands meeting: The CEO crowed about how their new Anti-depressant was doing well; "It has a very high rate of acceptance and a very low abandonment rate". In other words: Rapidly and aggressively addictive with fast and brutal withdrawal effects.

Overall the pharma industrie's products breakdown into 3 categories for me:~5% are Life Saving Medications that I would not want to live in a world without.~10 are quality of life enhancing.remaining ~85% are pure snake oil. And this is a substantial improvement over the past 100+ years of having the FDA in existence.

One thing I haven't seen discussed yet is getting data after the trials. If every doctor/patient would fill up a database with each persons results (both positive and negative) for each prescription they were prescribed, it could result in much better long term targeting of prescriptions. It would certainly improve the documentation on edge cases.

Of course, this doesn't address the very real privacy issues/concerns such a system would create.

One of the things that the medical profession in the UK has been doing right for years is the yellow card scheme: ever since the thalidomide disaster doctors, dentists, more recently nurses, pharmacists and coroners and, in the last half-decade, patients have been encouraged to report suspected adverse drug reactions to the MHRA (and its predecessors); the MHRA then collate these reports - about 20 000 are submitted per year - and uses them to identify "new signals (or potential safety concerns) such as a previously unrecognised side effect or ADR related to a specific drug. It also helps to confirm a signal of an ADR with limited information from an alternative data source, such as the literature or post-marketing studies, and also in evaluating comparative risks of related drugs"

In general, anonymised aggregate data is available on MHRA's website. More detailed information (including information with privacy implications) is available to researchers if the relevant ethical committees approve.

The main problem is not money or greed. Actually the system works quite well given the constraints.

But health is just hard. Hell it is not even possible to get consensus on some pretty basic foods if they are healthy or not:

Just a couple of examples:

Cholesterol: First the devil, now we realize that there is good and bad cholesterol, the body manages its own so eaten cholesterol doesn't really matter unless you have some specific problems then it suddenly matters again.

Salt: Does it influence blood pressure? Doesn't it? Apparently it also depends a lot on your physical condition, if you have health problems anyway it seems to hurt otherwise it doesn't really correlate with blood pressure.

Corn Syrup: On that one we could write books

Fruits/ juices: panacea of healthy living or sugary diabetis snack.

Hell you can write whole encyclopedias on the health benefits/problems of pretty much anything from fat, sugars, proteins, too much vitamins etc. pp.

The problem is that our body is awfully complex and answers often are a non satisfactory "it depends" (on your health, your genetics, quantities, lifestyle, other things you eat ... )

why should that be different for drugs? It is different if we are talking about drugs that target a very specific problem with a clear end result. A creme for a rash or antibiotics for example where you can do a real significant study that results in clearly defined results. But many of the modern drugs are lifestyle drugs that target long-term diseases like hypertony and here we have the same set of problems we have with food. It all is terribly complex.

So are pharma companies evil and want to make money? Up to a point sure and its good to stand on their toes but we should keep the complexity of the topic and the danger of hyperbole in mind. It may in General be a good idea to be a bit conservative when allowing new drugs on the other hand if you are suffering from a crippling illness you may not take conservatism very postiviely.

The Social Transformation of American Medicine by Paul Starr also does a pretty good job setting out why we can't let rationally self-interested people be in charge of healthcare.

There are a few things every human being needs to understand about doctors and medicine in general. This should be taut in every school, I think.

(1) Doctors are not your friends. They are never, ever, ever your friends. You might have a friend who is a doctor, but if that person is also YOUR doctor, then at the very most he is not your friend when he is also being your doctor. THAT SAID(2) If you are disappointed with your doctor's performance, you need to CHANGE DOCTORS.(3) If a doctor botches a surgery and then makes probability-based excuses that you were not informed of prior to surgery, you need to sue him for malpractice.(4) If you decide to sue a doctor for malpractice, do not settle prior to filing. This would keep doctors off the malpractice database. If you absolutely have to settle for financial reasons, you should at least hit up some consumer-review websites and inform them of the sued doctor's shortcomings.

LISTEN. Adverse medical events that could qualify as malpractice are hideously under-reported and not acted upon nearly enough. One of the reasons for this is that people trust their doctors, and believe post-hoc rationalizations for unseemly outcomes. This decreases tort liability as a means of controlling quality of healthcare.

You cannot trust anyone that has a rational self-interest in getting you out the door as quickly as possible or selling you a pill that might give you a goddamn heart attack.

UNLESS that Doctor has a time machine. Then you should probably do whatever he says.

Cholesterol: First the devil, now we realize that there is good and bad cholesterol, the body manages its own so eaten cholesterol doesn't really matter unless you have some specific problems then it suddenly matters again.

Actually no. Now we realize that most likely cholesterol is not actually directly related to heart disease in most cases, but is rather a symptom, not a cause. In other words, you have high cholesterol for the same reasons you have heart disease, but directly changing your cholesterol levels (as some drugs do) don't actually make a difference in your heart disease.

We have wonderful cholesterol lowering drugs which don't seem to actually lower mortality from heart disease in the people taking them. Whoops.

Quote:

(3) If a doctor botches a surgery and then makes probability-based excuses that you were not informed of prior to surgery, you need to sue him for malpractice.

This is not necessarily a good practice. Stupid lawsuits because people get unlucky is a major problem with the health industry. They need to fix you, sure, and pay for it, but suing them? Only if they don't pay for things going bad.

At the same time, I'm not sure the government would do much better. The greater good is in things like Viagra. It fixed a problem for millions of people, it was actually an amazing social breakthrough, the kind of thing a government would love to do to support the reason why they spend billions on research. The only difference would be that they hopefully wouldn't spend billions more trying to come up with a competitor, but the difference between a cash cow and something that helps win elections isn't all that far apart, really.

Viagra was an accident. It was intended (and tested) as heart medication and it had unexpected side effects. No money was spend on a cure for male impotence, although I believe other drug companies spent some developing their own version of viagra after it's accidental discovery.

and then there's the thing where a week's worth of "prescription strength" ibuprofen costs several times more than a huge bottle of generic advil. I got a prescription for that once and the pharmacist told me to just buy the generic and take 4 at a time because it'd be cheaper than my prescription copay.

You'd be surprised how many patients ask for a prescription to get ibuprofen. Medicare/Medicaid covers it outright so there's little incentive for people covered under those plans to buy over-the-counter.

I get (every so often) 2 bottles of 500 ibuprofen (shrink wrapped together) from Costco for about $10 or so. You can get many generics very cheaply, and not just at Costco.